Abstract
P. gingivalis is a major pathogen that is involved in the onset and progression of periodontal disease. This study investigated the effect of resveratrol, a naturally occurring polyphenol, on P. gingivalis LPS-accelerated vascular inflammation, a key step in the progression of periodontitis. Resveratrol significantly inhibited the P. gingivalis LPS-induced adhesion of leukocytes to endothelial cells and to the aortic endothelium by down-regulating the cell adhesion molecules, ICAM-1 and VCAM-1. Moreover, the inhibition of the P. gingivalis LPS-induced cell adhesion molecules by resveratrol was mainly mediated by nuclear factor-κB (NF-κB). Resveratrol suppressed P. gingivalis LPS-stimulated IκBα phosphorylation and nuclear translocation of the p65 subunit of NF-κB in HMECs. Overall, these findings suggest that resveratrol significantly attenuates the P. gingivalis LPS-induced monocyte adhesion to the endothelium by suppressing the expression of the NF-κB-dependent cell adhesion molecules, suggesting its therapeutic role in periodontal pathogen-induced vascular inflammation.
Similar content being viewed by others
References
Amar, S. and Han, X., The impact of periodontal infection on systemic diseases. Med. Sci. Monit., 9, RA291–9 (2003).
Coats, S. R., Reife, R. A., Bainbridge, B. W., Pham, T. T., and Darveau, R. P., Porphyromonas gingivalis lipopolysaccharide antagonizes escherichia coli lipopolysaccharide at toll-like receptor 4 in human endothelial cells. Infect. Immun., 71, 6799–6807 (2003).
Csiszar, A., Smith, K., Labinskyy, N., Orosz, Z., Rivera, A., and Ungvari, Z., Resveratrol attenuates TNF-alpha-induced activation of coronary arterial endothelial cells: Role of NF-kappaB inhibition. Am. J. Physiol. Heart Circ. Physiol., 291, H1694–9 (2006).
Cucciolla, V., Borriello, A., Oliva, A., Galletti, P., Zappia, V., and Della Ragione, F., Resveratrol: From basic science to the clinic. Cell. Cycle, 6, 2495–2510 (2007).
Das, S. and Das, D. K., Anti-Inflammatory Responses of Resveratrol. Inflamm. Allergy Drug Targets, 6, 168–173 (2007).
Demmer, R. T. and Desvarieux, M., Periodontal infections and cardiovascular disease: The heart of the matter. J. Am. Dent. Assoc. 137Suppl, 14S–20S; quiz 38S (2006).
Dong, Z., Molecular Mechanism of the Chemopreventive Effect of Resveratrol. Mutat. Res., 523–524, 145–150 (2003).
Egelberg, J., The Blood vessels of the dento-gingival junction. J. Periodontal. Res., 1, 163–179 (1966).
Ford, P. J., Gemmell, E., Timms, P., Chan, A., Preston, F. M., and Seymour, G. J., Anti-P. gingivalis response correlates with atherosclerosis. J. Dent. Res., 86, 35–40 (2007).
Gibson, F. C., Yumoto, H., Takahashi, Y., Chou, H. H., and Genco, C. A., Innate immune signaling and porphyromonas gingivalis-accelerated atherosclerosis. J. Dent. Res., 85, 106–121 (2006).
Gusman, J., Malonne, H., and Atassi, G., A reappraisal of the potential chemopreventive and chemotherapeutic properties of resveratrol. Carcinogenesis, 22, 1111–1117 (2001).
Hao, H. D. and He, L. R., Mechanisms of cardiovascular protection by resveratrol. J. Med. Food 7, 290–298 (2004).
Hirschfeld, M., Weis, J. J., Toshchakov, V., Salkowski, C. A., Cody, M. J., Ward, D. C., Qureshi, N., Michalek, S. M., and Vogel, S. N., Signaling by toll-like receptor 2 and 4 agonists results in differential gene expression in murine macrophages. Infect. Immun., 69, 1477–1482 (2001).
Holmes-McNary, M. and Baldwin, A. S. Jr., Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the IkappaB kinase. Cancer Res., 60, 3477–3483 (2000)
Karin, M. and Ben-Neriah, Y., Phosphorylation meets ubiquitination: The control of NF-[Kappa]B activity. Annu. Rev. Immunol., 18, 621–663 (2000).
Kim, S. R., Bae, Y. H., Bae, S. K., Choi, K. S., Yoon, K. H., Koo, T. H., Jang, H. O., Yun, I., Kim, K. W., Kwon, Y. G. et al., Visfatin enhances ICAM-1 and VCAM-1 expression through ROS-dependent NF-kappaB activation in endothelial cells. Biochim. Biophys. Acta, 1783, 886–895 (2008).
Kundu, J. K., Shin, Y. K., Kim, S. H., and Surh, Y. J., Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NF-kappaB in mouse skin by blocking IkappaB kinase activity. Carcinogenesis, 27, 1465–1474 (2006).
Kundu, J. K. and Surh, Y. J., Cancer chemopreventive and therapeutic potential of resveratrol: Mechanistic perspectives. Cancer Lett. (2008).
Ley, K., Laudanna, C., Cybulsky, M. I. and Nourshargh, S., Getting to the site of inflammation: The leukocyte adhesion cascade updated. Nat. Rev. Immunol., 7, 678–689 (2007).
Manna, S. K., Mukhopadhyay, A., and Aggarwal, B. B., Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappa B, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. J. Immunol., 164, 6509–6519 (2000)
Mao, S., Maeno, N., Matayoshi, S., Yoshiie, K., Fujimura, T., and Oda, H., The induction of intercellular adhesion molecule-1 on human umbilical vein endothelial cells by a heat-stable component of porphyromonas gingivalis. Curr. Microbiol., 48, 108–112 (2004).
Minami, T. and Aird, W. C., Thrombin stimulation of the vascular cell adhesion molecule-1 promoter in endothelial cells is mediated by tandem nuclear factor-kappa B and GATA motifs. J. Biol. Chem., 276, 47632–47641 (2001).
Nakamura, N., Yoshida, M., Umeda, M., Huang, Y., Kitajima, S., Inoue, Y., Ishikawa, I. and Iwai, T., Extended exposure of lipopolysaccharide fraction from porphyromonas gingivalis facilitates mononuclear cell adhesion to vascular endothelium via toll-like receptor-2 dependent mechanism. Atherosclerosis, 196, 59–67 (2008).
Page, R. C. and Schroeder, H. E., Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab. Invest., 34, 235–249 (1976).
Rahman, I., Biswas, S. K., and Kirkham, P. A., Regulation of inflammation and redox signaling by dietary polyphenols. Biochem. Pharmacol., 72, 1439–1452 (2006).
Rao, R. M., Yang, L., Garcia-Cardena, G., and Luscinskas, F. W., Endothelial-dependent mechanisms of leukocyte recruitment to the vascular wall. Circ. Res., 101, 234–247 (2007).
Slots, J. and Ting, M., Actinobacillus actinomycetemcomitans and porphyromonas gingivalis in human periodontal disease: Occurrence and treatment. Periodontol. 2000 20, 82–121 (1999).
Tsai, S. H., Liang, Y. C., Lin-Shiau, S. Y., and Lin, J. K., Suppression of TNFalpha-mediated NFkappaB activity by myricetin and other flavonoids through downregu=-lating the activity of IKK in ECV304 cells. J. Cell Biochem., 74, 606–615 (1999)
Walter, C., Zahlten, J., Schmeck, B., Schaudinn, C., Hippenstiel, S., Frisch, E., Hocke, A. C., Pischon, N., Kuramitsu, H. K., Bernimoulin, J. P., Suttorp, N., and Krull, M., Porphyromonas gingivalis strain-dependent activation of human endothelial cells. Infect. Immun., 72, 5910–5918 (2004).
Wang, P. L. and Ohura, K., Porphyromonas gingivalis lipopolysaccharide signaling in gingival fibroblasts-CD14 and toll-like receptors. Crit. Rev. Oral Biol. Med., 13, 132–142 (2002).
Wang, P. L., Oido-Mori, M., Fujii, T., Kowashi, Y., Kikuchi, M., Suetsugu, Y., Tanaka, J., Azuma, Y., Shinohara, M. and Ohura, K., Heterogeneous expression of toll-like receptor 4 and downregulation of toll-like receptor 4 expression on human gingival fibroblasts by porphyromonas gingivalis lipopolysaccharide. Biochem. Biophys. Res. Commun., 288, 863–867 (2001).
Youn, H. S., Lee, J. Y., Fitzgerald, K. A., Young, H. A., Akira, S., and Hwang, D. H., Specific inhibitor of MyD88-indepent signaling pathways of TLR3 and TLR4 by resveratrol: molecular targets are TBK1 and RIP1 in TRIF complex. J. Immunol., 175, 3339–3346 (2005)
Yun, P. L., Decarlo, A. A., Chapple, C. C., and Hunter, N., Functional implication of the hydrolysis of platelet endothelial cell adhesion molecule 1 (CD31) by gingipains of porphyromonas gingivalis for the pathology of periodontal disease. Infect. Immun., 73, 1386–1398 (2005).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Park, HJ., Jeong, SK., Kim, SR. et al. Resveratrol inhibits Porphyromonas gingivalis lipopolysaccharide-induced endothelial adhesion molecule expression by suppressing NF-κB activation. Arch. Pharm. Res. 32, 583–591 (2009). https://doi.org/10.1007/s12272-009-1415-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-009-1415-7